PROJECT SUMMARY Infertility is a common condition affecting as many as 15% of couples in the United States. Despite its prevalence, little is known about the determinants of infertility overall, or on modifiable risk factors for the male and female contributions to infertility. Male factors (commonly defined clinically as abnormalities in conventional semen quality parameters) are implicated in as many as 58% of cases, with an additional one third of cases attributed to both male and female factors. Genetics have been shown to account for a small percent (10-15%) of male infertility, indicating that lifestyle factors and environmental exposures likely play a vital role in the majority of male factor infertility cases. Compelling animal and human studies have linked exposures to air pollution with altered semen quality. A recent review and a recent meta-analysis of the human epidemiologic data both concluded that air pollution has been associated with various measures of semen quality, but both pointed to issues of comparability, consistency, and quality in the existing literature. Concerns have also been raised regarding the impacts of environmental exposures to endocrine disrupting chemicals (EDCs), including phthalates, flame retardants, pesticides, volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) as well as the implications of exposures to multiple chemicals simultaneously. Although the results of this literature are compelling, a number of important research gaps remain. To date, no study has comprehensively examined the impact of multiple environmental exposures from a wide variety of sources among groups of young, otherwise healthy men, and little is known regarding the potential epigenetic changes these exposures may make to spermatozoa that may lead to adverse health effects in later generations. Our proposed study will address a number of these limitations, while taking advantage of newly available mobile monitoring devices, novel outcome measurement techniques, and newly developed real-time exposure monitoring and passive personal samplers to improve exposure assessment. We will leverage these combined technologies in the Growing Up Today Study (GUTS), a prospective nationwide cohort of young adults followed since early childhood. Ambient and in-home measures of air pollution will be assigned throughout spermatogenesis and personal exposures to a wide range of EDCs will be assessed with personal passive wristbands. We will assess the impact of multiple environmental exposures on measures of semen quality (concentration, total count, and motility) assessed via cell phone, morphology assessed with standard laboratory methods, and novel epigenomic markers (sperm DNA methylation). Specifically we will evaluate the associations of ambient and indoor home exposures to PM2.5 and NO2 and personal measurements of EDCs on semen quality (concentration, count, morphology, and motility) and assess the association of these exposures on sperm DNA methylation patterns.